Pachymic acid ameliorates bleomycin-induced pulmonary fibrosis through inhibiting endoplasmic reticulum stress in rats

Lin Li; Rong-Jie Jin; Lu Ji

doi:10.1002/tox.23824

Pachymic acid ameliorates bleomycin-induced pulmonary fibrosis through inhibiting endoplasmic reticulum stress in rats

Environ Toxicol. 2023 May 10. doi: 10.1002/tox.23824. Online ahead of print.

Authors

Lin Li¹, Rong-Jie Jin², Lu Ji³

Affiliations

¹ Respiratory department, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
² Department of security, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
³ Department of Radiology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.

PMID: 37163307
DOI: 10.1002/tox.23824

Abstract

The effect of pachymic acid (PA) on pulmonary fibrosis in rats was expected to be investigated in this study. Firstly, bleomycin (BLM) was used to establish pulmonary fibrosis rat model, then PA (10, 20, or 40 mg/kg) was intragastrically administered to the rats for 14 days. Subsequently, a variety of tests was performed to observe changes in sample tissues after different treatments. Briefly, the degree of pulmonary edema in rats was assessed through dry/wet weight ratio. Hematoxylin and eosin (H&E) staining and Masson's trichrome staining were used to observe the pathological injury and fibrosis of lung tissue. Biochemical kits were applied to measure the levels of hydroxyproline (Hyp), transforming growth factor beta-1 (TGFβ-1), malondialdehyde (MDA), reactive oxygen species (ROS), and adenosine triphosphate (ATP) and the activities of superoxide dismutase (SOD) and catalase (CAT) in rat lung tissues of each group. The mitochondrial DNA (mtDNA) copy number in rat lung tissue was tested using qRT-PCR. Additionally, the western blot was employed to detect the expression levels of pulmonary fibrosis-related proteins and endoplasmic reticulum (ER) stress-related proteins in each group of rat lung tissue. By virtue of experimental verification above, PA was discovered to alleviate BLM-induced pulmonary edema, pulmonary fibrosis and histopathological damage. On the one hand, PA treatment decreased Hyp and TGF-β1 levels and down-regulated pulmonary fibrosis-related protein expression [collagen I, α-smooth muscle actin (α-SMA), and fibronectin] in the lung tissue of BLM rats. On the other hand, it significantly increased the levels of SOD, CAT and ATP while decreased the activities of MDA and ROS in BLM rat lung tissues. In addition, the expression levels of ER stress-related proteins [glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), Caspase 9, and activating transcription factor 4 (ATF4)] were significantly down-regulated in the lung tissue of BLM rats after PA treatment. Collectively, PA may ameliorate BLM-induced pulmonary fibrosis and histopathological damage in rats through inhibiting ER stress and improving mitochondrial function.

Keywords: endoplasmic reticulum (ER) stress; mitochondria; oxidative stress; pachymic acid (PA); pulmonary fibrosis.